The development of a comprehensive series of anti-viral assays has facilitated the biological characterization of new lead compounds initially identified using the NCI primary anti-HIV screen. The assays define specific stages in the HIV life cycle and include a diverse set of biochemical endpoints. Implementation of these assays has facilitated the prioritization of new lead synthetic compounds as well as natural product-derived compounds for preclinical development. During the present report year we have focused particularly upon non-nucleoside inhibitors of HIV reverse transcriptase.